Histiocytic DisordersPhase 2NCT02649972
Single-agent Cobimetinib for Adults With Histiocytic Disorders
A Phase 2 study testing Cobimetinib in people with Histiocytic Disorders, run by Memorial Sloan Kettering Cancer Center at 2 sites in United States.
Trial summary
The purpose of this study is to find out what effects, good or bad, Cobimetinib has in patients with histiocytosis. Cobimetinib is an investigational oral medication that blocks MEK1. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Histiocytic Disorders
- What is being tested?
- Cobimetinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2016to 16 Dec 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically confirmed histiocytic disorder or histologic findings compatible with a histiocytic disorder in the context of confirmatory radiologic findings confirmed by the enrolling institution.
- One of the following:
- Documentation of BRAF V600E mutation and inability to access of BRAF inhibitor or prior treatment with a BRAF inhibitor discontinued due intolerable side effects or toxicity prior to progression, -OR-
- Documentation of wild-type BRAF V600 mutational status
- Patients with BRAF-mutated ECD/LCH who have had disease progression on BRAF inhibitor therapy would be eligible but would require tissue biopsy (or available tissue) for genotyping before participating.
- Measurable disease according to PET Response Criteria, confirmed by the MSK investigator radiologist, with the exception of patients with cutaneous disease that can be measured and followed by RECIST criteria
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- Histiocytic disorder must be (a) multi-system disease or (b) disease that is recurrent or refractory to standard therapies, or (c) single-system disease with that is unlikely to benefit from conventional and less toxic therapies, based on the best available evidence (for example, CNS or cardiac infiltration, retroperitoneal fibrosis, prior chemotherapy, or other medical history or co-morbidities, etc)
- Life expectancy > 12 weeks
- Age ≥ 16 years
- ECOG performance status ≤ 3 (May be converted from Karnofsky Performance Status)
- Adequate bone marrow function as indicated by the following:
- ANC > 1000/uL
- Platelets ≥ 50,000/uL
- Hemoglobin ≥ 8.5 g/dL.
- Patients with cytopenias below these thresholds deemed to be the result of disease will be considered eligible.
- Adequate renal function, as indicated by:
- creatinine ≤ 1.5 the upper limit of normal (ULN) -OR-
- Estimated creatinine clearance of > 50 ml/min
- As for #7, patients with renal dysfunction deemed to be the result of disease will be considered eligible.
- Adequate liver function, as defined by bilirubin ≤ 1.5 ULN
- AND AST/ALT < 3 ULN
- Ability to swallow pills
- Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year.
- Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
- Patients must be willing to consent for protocol #12-245 for IMPACT testing (for MSK patients ONLY).
Who cannot join
- Prior treatment with a MEK inhibitor
- Active infection requiring intravenous antibiotics
- Pregnant, lactating or breast feeding women
- Prior radiation therapy within the last 14 days
- Unwillingness or inability to comply with study and follow-up procedures.
- Any foods/supplements that are strong inhibitors or inducers of CYP3A are prohibited at least 7 days prior to initiation of and during study treatment
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- History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, RVO, or neovascular macular degeneration
- The risk factors for RVO are listed below. Exclusion should be considered by clinical discretion if they have the following conditions:
- Uncontrolled glaucoma with intra-ocular pressures > 21mmHg
- Serum cholesterol ≥ Grade 2
- Hypertriglyceridemia ≥ Grade 2
- Hyperglycemia ≥ Grade 2
- History of clinically significant cardiac dysfunction, unless deemed to be the direct result of disease, including the following:
- Current unstable angina
- Symptomatic congestive heart failure of NYHA class 2 or higher
- Uncontrolled hypertension ≥ Grade 2 (patients with a history hypertension controlled with anti-hypertensives to ≤ Grade 2 are eligible).
- Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or below 50%
- Uncontrolled arrhythmias
- Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous 6 months
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: Phase II Trial of Single-agent Cobimetinib for Adults With Histiocytic Disorders
The purpose of this study is to find out what effects, good or bad, Cobimetinib has in patients with histiocytosis. Cobimetinib is an investigational oral medication that blocks MEK1.
- Conditions
- Histiocytic Disorders
- Being tested
- Cobimetinib
- Keywords
- Cobimetinib, 15-216
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CobimetinibDrug
Cobimetinib will be administered at a dose of 60mg daily for 21 days on, then 7 days off, in a 28 day treatment cycle. Patients will have the option to discontinue treatment after 12 cycles and will be monitored for disease relapse for an additional 12 months. In the event that disease relapse occurs within the 12 month monitoring period, patients will restart treatment and continue on study. Upon restarting, the assessment schedule will restart at rechallenge cycle 1(RC-1) and all assessments will occur at the frequency and intervals. Cycle 1 Day 15 visits will not be required for patients that restart treatment after relapse. Participants will re-sign consent upon rechallenging.
| Study group | Role | What they receive |
|---|---|---|
| Cobimetinib | Experimental | This is an open-label, multicenter, phase II study exploring the efficacy and safety of single-agent Cobimetinib in patients with histiocytic disorders whose tumors are 1) BRAFV600 wildtype or 2) BRAFV600E mutant and are intolerant to, or unable to access, BRAF inhibitors. Visits during the treatment period are to be completed on Day 1, Day 15 (this visit can be by telephone), Day 29, and every 28 days thereafter. For patients treated on the study for six months, at the discretion of the Principal Investigator, visits can be spaced out to every 56 days (every 2 cycles instead of every cycle). After 24 cycles of treatment, if imaging demonstrates sustained stability in the opinion of the principal investigator, tumor assessments can be performed ever 1 year. Receives: Drug: Cobimetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response
by PET Response Criterial (PRC), with a dichotomous BOR of CR or PR versus neither of those. Assuming we use this binary endpoint of response, defined as best overall response of CR or PR versus not using the PET Response Criteria (PRC), a sample size of 18 patients provides 90% power to test the hypothesis that the response rate is promising (defined as 35% or higher) against a non-promising rate of 10% or lower.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2016 (estimated)
- Study startJan 2016
- Primary completion16 Dec 2022
- Study completion16 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Histiocytic DisordersStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Eli Diamond, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02649972
- Sponsor's protocol ID
- 15-216
- Status last verified
- Dec 2022
- First submitted
- 6 Jan 2016
- Last updated
- 18 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Single-agent Cobimetinib for Adults With Histiocytic Disorders
- ClinicalTrials.gov ID
- NCT02649972
- Acronym / sponsor ID
- 15-216
- Conditions
- Histiocytic Disorders
- Keywords
- Cobimetinib, 15-216
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jan 2016 (actual)
- Primary completion
- 16 Dec 2022 (actual)
- Study completion
- 16 Dec 2022 (actual)
- First posted
- 8 Jan 2016 (estimated)
- Results
- Posted 18 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out what effects, good or bad, Cobimetinib has in patients with histiocytosis. Cobimetinib is an investigational oral medication that blocks MEK1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cobimetinib | Experimental | Drug: CobimetinibThis is an open-label, multicenter, phase II study exploring the efficacy and safety of single-agent Cobimetinib in patients with histiocytic disorders whose tumors are 1) BRAFV600 wildtype or 2) BRAFV600E mutant and are intolerant to, or unable to access, BRAF inhibitors. Visits during the treatment period are to be completed on Day 1, Day 15 (this visit can be by telephone), Day 29, and every 28 days thereafter. For patients treated on the study for six months, at the discretion of the Principal Investigator, visits can be spaced out to every 56 days (every 2 cycles instead of every cycle). After 24 cycles of treatment, if imaging demonstrates sustained stability in the opinion of the principal investigator, tumor assessments can be performed ever 1 year. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- Histologically confirmed histiocytic disorder or histologic findings compatible with a histiocytic disorder in the context of confirmatory radiologic findings confirmed by the enrolling institution.
- One of the following:
- Measurable disease according to PET Response Criteria, confirmed by the MSK investigator radiologist, with the exception of patients with cutaneous disease that can be measured and followed by RECIST criteria
- Histiocytic disorder must be (a) multi-system disease or (b) disease that is recurrent or refractory to standard therapies, or (c) single-system disease with that is unlikely to benefit from conventional and less toxic therapies, based on the best available evidence (for example, CNS or cardiac infiltration, retroperitoneal fibrosis, prior chemotherapy, or other medical history or co-morbidities, etc)
- Life expectancy > 12 weeks
Key exclusion criteria (19 listed)
- Prior treatment with a MEK inhibitor
- Active infection requiring intravenous antibiotics
- Pregnant, lactating or breast feeding women
- Prior radiation therapy within the last 14 days
- Unwillingness or inability to comply with study and follow-up procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CobimetinibCobimetinib will be administered at a dose of 60mg daily for 21 days on, then 7 days off, in a 28 day treatment cycle. Patients will have the option to discontinue treatment after 12 cycles and will be monitored for disease relapse for an additional 12 months. In the event that disease relapse occurs within the 12 month monitoring period, patients will restart treatment and continue on study. Upon restarting, the assessment schedule will restart at rechallenge cycle 1(RC-1) and all assessments will occur at the frequency and intervals. Cycle 1 Day 15 visits will not be required for patients that restart treatment after relapse. Participants will re-sign consent upon rechallenging. | Drug | Cobimetinib |
Primary outcome
Best Overall Response
Time frame: 1 year
by PET Response Criterial (PRC), with a dichotomous BOR of CR or PR versus neither of those. Assuming we use this binary endpoint of response, defined as best overall response of CR or PR versus not using the PET Response Criteria (PRC), a sample size of 18 patients provides 90% power to test the hypothesis that the response rate is promising (defined as 35% or higher) against a non-promising rate of 10% or lower.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eli Diamond, MD principal investigator
Memorial Sloan Kettering Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cobimetinib in people with Histiocytic Disorders, run by Memorial Sloan Kettering Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.